Thread for vascular stent and vascular stent using the thread

ABSTRACT

A thread ( 1 ) for forming a vascular stent implanted in vessels. This thread is formed by melt-spinning a biodegradable polymer. On the surface of the thread, there is formed a layer ( 2 ) of a drug-containing biodegradable polymer of the same sort as the biodegradable polymer constituting the thread.

TECHNICAL FIELD

This invention relates to a thread for forming a stent for vessels,implanted within vessels of a living body, such as lymph vessels, bileducts or ureter, for maintaining a patency state of the lumen of thevessels, and to a stent for vessels employing the thread.

This application claims priority of Japanese Patent ApplicationNo.2002-279404, filed in Japan on Sep. 25, 2002, the entirety of whichis incorporated for reference herein.

BACKGROUND ART

In angioplasty, mechanical techniques, such as balloon dilationtechnique or stent implanting technique, tend to injure blood vessels.In a site of lesion of the blood vessels, acute coronary occlusion,caused by thrombosis, or re-stenosis, caused by intimal hyperplasia ofthe blood vessel, as a curative reaction of the wall of the bloodvessel, occurs frequently.

In acute coronary occlusion, thrombosis plays some role. For possibleprevention, antithrombotic therapy by systemic administration of drugsvia veins is customarily used.

On the other hand, re-stenosis is induced by excess hyperplasia ofcells. Currently, researches into drugs for suppressing hyperplasia ofcells are going on briskly, and several drugs have been found as givingacceptable results.

For deriving favorable results of these pharmaceuticals, it is necessaryto administer the drugs at/in a high concentration or in a largequantity. It has, however, been indicated that side effects tend to beproduced by such administration.

Recently, a local drug delivery system (LDDS) has come to be used as asafe and efficacious method for possible prevention of acute coronaryocclusion or re-stenosis. In this LDDS, a stent is stirring up notice asa member for transporting the drug to a target site of the blood vessel.With the LDDS, employing the stent, local administration of the drugbecomes possible by implanting the stent, carrying the drug, in a targetsite in the blood vessel. The stent can be implanted in a target site inthe blood vessel, without obstructing the blood flow, for a prolongedtime, and hence can be used as the LDDS which may produce a sufficientpharmaceutical effect for a prolonged period of time.

Meanwhile, the majority of the stents for blood vessels, used at presentfor clinical purposes, are made of metal. With metal, the drug cannot bemixed into the material, such that the drug can be applied only to itssurface. Among a variety of methods for depositing the drug to the metalstent, there are a coating method and a bonding method, as disclosed inthe Japanese Laid-Open Patent Publication H-8-33718. When the drug isdeposited on the surface of the metal stent by the coating method or thebonding method, there is raised a problem that the drug itself may peeloff from the stent surface. Furthermore, it is difficult to deposit anamount of the drug sufficient to derive the pharmaceutical effect. Inaddition, since the metal stent, implanted in the blood vessel, remainspermanently as a foreign substance, there is a possibility thatre-stenosis may be produced in the stent implant site of the bloodvessel.

With the LDDS, it is necessary to control the content of the drug, theamount of drug release per unit time and the time period of drugrelease. In order to take precautions against acute coronary occlusionor re-stenosis by the LDDS more effectively, such control is desirablein which the effective concentration of the drug in the target bloodvessel site may be maintained and in which the drug may be released fora predetermined period to the blood vessel wall and into the blood.

DISCLOSURE OF THE INVENTION

It is an object of the present invention to provide a thread for forminga stent for vessels, and a stent for vessels, in which the drug can bereliably retained to implant in the vessel, such as blood vessel.

It is another object of the present invention to provide a thread forforming a stent for vessels, and a stent for vessels, in which the drugcan be released into the body of for a prolonged period of time.

It is a further object of the present invention to provide a thread forforming a stent for vessels, and a stent for vessels, in which it ispossible to control the drug content, the amount of drug release perunit time, and the time period for drug=release.

It is yet another object of the present invention to provide a threadfor forming a stent for vessels, which thread is degraded in vivo afteror in the course of drug release without being left as a foreignsubstance in the living body, and a stent for vessels.

The present invention, proposed for accomplishing the above objects, isdirected to a thread for forming a stent for vessels introduced andimplanted in vessels, such as blood vessels, in a living body, andcomprises a thread formed on melt-spinning a biodegradable polymer and alayer of a biodegradable polymer containing a drug and which is of thesame sort as the biodegradable polymer constituting the thread. Abiodegradable polymer, in which to contain the drug, is dissolved onbeing mixed with a solvent, to yield a solution. A drug is mixed ordissolved in this solution of the biodegradable polymer. The solution ofthe biodegradable polymer, into which the drug is mixed or dissolved, iscoated on the thread surface to constitute the drug-containing layer.

The biodegradable polymer, constituting the drug-containing layer, is ofthe same sort as the biodegradable polymer constituting the thread, andhence is deposited on the thread surface with superior tight adhesiveproperties. In addition, since the biodegradable polymer constitutingthe drug-containing layer, is of the same sort as the biodegradablepolymer constituting the thread, it may be considered that the twopolymers are degraded in vivo with substantially the same speed.

The biodegradable polymer constituting the thread is e.g. an aliphaticpolyester. The aliphatic polyester may be enumerated by poly (α-hydroxyacid), such as polyglycolic acid or poly-L-lactic acid, andpoly(ω-hydroxyalkanoates), such as poly-ε-caprolactone. Hence, this sortof the aliphatic polyester is also used as the biodegradable polymerconstituting the drug-containing layer.

The thread for the stent for vessels, according to the presentinvention, may be a monofilament, obtained on melt-spinning abiodegradable polymer. It may also be a multifilament, obtained in thesame manner.

As the drug contained in the biodegradable polymer, deposited on thethread surface, such drug exhibiting antithrombotic effect and/orintimal hyperplasia suppressing effect, may be used. The drug exhibitingthe intimal hyperplasia suppressing effect may be an immunosuppressiveagent or an anticancer agent. An example of the drug exhibiting theintimal hyperplasia suppressing effect is Tranilast[N-(3,4-dimethoxycinnamoyl) anthranilic acid]. The immunosuppressiveagent used may be rapamycin (Sirolimus), while the anticancer agent usedmay be taxel (Paclitaxel).

In the thread for a stent for vessels according to the presentinvention, a second layer, formed only of the biodegradable polymer ofthe same sort as the biodegradable polymer, constituting the thread, isdeposited on a first layer of the drug-containing biodegradable polymer.By providing the second layer, formed only of the biodegradable polymer,on the drug-containing first layer, it becomes possible to suppress thetime period of release of the drug contained in the first layer, by wayof extending the drug release time duration.

In another thread for a stent for vessels, according to the presentinvention, a drug is mixed into a biodegradable polymer, on the surfaceof which is formed a layer of a biodegradable polymer of the same sortas the drug-containing biodegradable polymer constituting the thread.

As the drug contained in the thread provided with the drug-containinglayer, such a drug exhibiting the antithrombotic effect and/or intimalhyperplasia suppressing effect, similar to that exhibited by the drugcontained in the drug-containing layer, may be used.

The drug-containing layer, formed on the thread surface, is formed bycoating the thread surface with a biodegradable polymer solution, inwhich the drug has been mixed or dissolved, as described above.

With the thread for a stent for vessels, containing the drug, the secondlayer of a biodegradable polymer of the same sort as the biodegradablepolymer, constituting the thread, may be formed on the drug-containingfirst layer of the biodegradable polymer. This second layer is formed oncoating the first layer with the solution of the biodegradable polymer.

The present invention provides a stent for vessels formed usingabove-described threads for a stent for vessels. The stent for vesselsis formed by the threads for a stent for vessels being wound to a tubeas each of the threads is bent in a zigzag design and is enlarged orcontracted in diameter with the bends of the threads as displacingportions.

With the thread constituting the main stent body, obtained onmelt-spinning a biodegradable polymer with a screw extruder and ondrawing the resulting product, a monofilament may be used. Amultifilament, obtained in the same manner, may also be used.

Since the stent for vessels, according to the present invention, isformed using a thread for a stent for vessels, provided with adrug-containing layer on the thread surface with good adhesiveproperties thereto, the drug is reliably delivered to and implanted in atarget site in a vessel, without peeling off from the stent in thecourse of insertion into the vessel.

Since the stent for vessels according to the present invention is formedusing the thread of the biodegradable polymer, it does not remain as aforeign substance in the living body and it is absorbed after a certainperiod of time.

With the stent for vessels, according to the present invention, abiodegradable polymer layer may be formed on the surface of the mainstent body unit, formed using the thread for a stent for vessels, bycoating the surface with a solution of the biodegradable polymer of thesame sort as the material constituting the thread.

By providing the biodegradable polymer layer on the surface of the mainstent body, in this manner, it is possible to suppress release of thedrug contained in the drug-containing layer to extend the drug releasetime duration.

Other objects and advantages of the present invention are revealed inthe following explanation of preferred embodiments thereof especiallywhen read in conjunction with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing a thread making up the thread forthe stent for vessels according to the present invention.

FIG. 2 is a perspective view showing another embodiment of the threadfor a stent for vessels according to the present invention.

FIG. 3 is a cross-sectional view showing the thread for a stent forvessels according to the present invention.

FIG. 4 is a cross-sectional view showing another embodiment of thethread for a stent for vessels according to the present invention.

FIG. 5 is a cross-sectional view showing still another embodiment of thethread for a stent for vessels according to the present invention.

FIG. 6 is a cross-sectional view showing yet another embodiment of thethread for a stent for vessels according to the present invention.

FIG. 7 is a plan view showing a stent for vessels according to thepresent invention.

FIG. 8 is a plan view showing the bent state of a thread for a stent forvessels making up a main stent body unit.

FIG. 9 is a plan view showing a portion of the main stent body unit toan enlarged scale.

FIG 10 is a perspective view showing the state of imparting shape memoryto the stent for vessels.

FIG. 11 is a plan view showing the bent state of a thread for a stentfor vessels when the stent for vessels is contracted in diameter.

FIG. 12 is a plan view showing the state of the stent for vesselscontracted in diameter.

BEST MODE FOR CARRYING OUT THE INVENTION

Referring to the drawings, a thread for a stent for vessels, and a stentfor vessels, employing the thread, are explained in detail.

The thread according to the present invention is used for forming astent for vessels, in particular a stent for blood vessels, used as itis inserted into the blood vessels, such as a coronary artery.

The thread used for forming a stent for vessels, according to thepresent invention, is formed of a biodegradable polymer which, whenimplanted in a living body, such as a human body, does not affect theliving body. As this biodegradable polymer, an aliphatic polyester isused. Specified examples of the aliphatic polyester include poly(α-hydroxy) acid, such as polyglycolic acid or polylactic acid, andpoly(ω-hydroxyalkanoates), such as poly-ε-caprolactam.

The thread formed of this sort of the biodegradable polymer may be spunusing a screw extruder. For spinning the thread by a screw extruder,pellets of the biodegradable polymer are first charged into a hopper ofthe screw extruder, and are compressed and melted, within a cylinder, asthe pellets are heated to a temperature in the vicinity of a meltingpoint Tm or to a temperature not lower than the melting point and nothigher than a thermal decomposition temperature. Within the cylinder, isrotated a screw on the outer periphery of which has been formed a spiralgroove. The biodegradable polymer, melted in the cylinder, is extrudedfrom a nozzle, set to a temperature not lower than the glass transitiontemperature Tg. The linear biodegradable polymer, extruded from thenozzle, is taken up with a take-up device. This linear biodegradablepolymer is further drawm when or after it is taken up with the take-updevice, to form a thread as a base material for a thread arn for a stentfor vessels according to the present invention.

The thread 1, as the base material for the thread for a stent forvessels, formed according to the present invention, is made up of acontinuous monofilament, as shown in FIG. 1.

The thread 1, as the base material for the thread for a stent forvessels, according to the present invention, may be formed not only of amonofilament, but also of a multifilament, composed of pluralmonofilaments 1 a, unified together, as shown in FIG. 2.

The thread 1 may not only be circular but also a flattened in across-sectional shape.

A thread 10 for a stent for vessels, according to the present invention,is formed from the thread 1, obtained on spinning the above-describedbiodegradable polymer, as the base material, as shown in FIG. 3.

On the surface of the thread 1, as the base material, there is provideda drug-containing layer 2, as a first layer of a drug-containingbiodegradable polymer, as shown in FIG. 3. The drug-containing layer 2is formed by coating the surface of the y thread rn 1 with a solutionobtained on mixing a drug in a biodegradable polymer dissolved with asolvent.

The biodegradable polymer, forming the drug-containing layer 2, is ofthe same sort of polymer as the biodegradable polymer forming the thread1. In case the thread 1 is formed of poly-L-lactic acid (PLLA), thebiodegradable polymer, forming the drug-containing layer 2, is formed ofthe same sort of polymer, that is, poly-L-lactic acid (PLLA). The samesort of the biodegradable polymer means the biodegradable polymer whichhas the same molecular branch and which may differ in molecular weight.For example, the thread 1 may be formed of a high molecular weightpoly-L-lactic acid (PLLA), while the drug-containing layer 2 may beformed of poly-L-lactic acid (PLLA) lower in molecular weight than thepoly-L-lactic acid (PLLA) of the thread 1.

As the drug contained in the drug-containing layer 2, such a drugexhibiting an antithrombotic effect and/or an intimal hyperplasiasuppressing effect may be used. As the drug exhibiting the intimalhyperplasia suppressing effect, an immunosuppressive agent or ananticancer agent may be used. As the drug having the intimal hyperplasiasuppressing effect, Tranilast [N-(3,4-dimethoxy cinnamoyl)anthranilic-acid] may be used. As the immunosuppressive agent and theanticancer agent, Lapamycin (Sirolimus) and taxel (Paciltaxel) may beused, respectively.

The solution forming the drug-containing layer 2 is prepared by heatingand dissolving pellets of the biodegradable polymer, as a solvent isadded thereto, and charging a drug into the dissolved biodegradablepolymer.

If poly-L-lactic acid (PLLA) is used as the biodegradable polymer,1,4-dioxane, used as a solvent, is added to pellets of poly-L-lacticacid (PLLA), and stirred for dissolution, as the reaction system isheated to approximately 90° C. A drug, such as Tranilast powders, isadded to the dissolved biodegradable polymer and stirred to produce adrug-containing solution.

Meanwhile, if poly-L-lactic acid (PLLA) is used as a biodegradablepolymer, dichloromethane is desirably used.

The drug-containing solution is coated on the surface of the thread 1,using a coating means, to form the drug-containing layer 2.

The thread 1, coated with the drug-containing solution, is rinsed at theoutset to remove impurities, such as dust and dirt, affixed to itssurface.

The thread 1 is rinsed with ethanol and distilled water. First, thethread 1 is charged into a rise tank, charged with ethanol, for rinsing.The thread 1, rinsed with ethanol, is charged into a rinse tank, chargedwith distilled water, for rinsing. The thread 1, thus rinsed, is thendried and coated with the drug-containing solution.

The drug-containing solution, constituting the drug-containing layer 2,has dissolved therein the same sort of the material as the biodegradablepolymer constituting the thread 1, on which the solution is coated, andhence is deposited to the thread 1 with satisfactory adhesiveproperties. The drug-containing layer 2, formed using this solution, isunified to and deposited on the surface of the thread 1 in a manner freefrom peeling or removal. Hence, the drug contained in thedrug-containing layer 2 is carried on the surface of the thread 1 in amanner free from peeling or removal.

By forming the stent for vessels, using the thread 10 for a stent forvessels, in which the drug-containing layer 2 is carried on the surfaceof the thread 1 in a manner free from peeling or removal, it becomespossible to administer the drug positively to a desired site in theliving body.

With the thread 10 for a stent for vessels, the amount of drug releaseper unit time may be varied by changing the amount of the drug containedin the drug-containing layer 2.

With a thread for a stent for vessels 20, according to the presentinvention, a second layer 3, formed only of the biodegradable polymer ofthe same sort as the biodegradable polymer constituting the thread 1,may be additionally deposited on the drug-containing layer 2, operatingas a first layer, as shown in FIG. 4.

The second layer 3 is formed of the same sort of the biodegradablepolymer, forming the thread 1, so that, in case the thread 1 is formedby poly-L-lactic acid, the second layer is formed of the same sort ofpoly-L-lactic acid. That is, the second layer 3 is formed ofpoly-L-lactic acid (PLLA) which is the same as the thread 1, or ofpoly-L-lactic acid (PLLA) lower in molecular weight than poly-L-lacticacid constituting the thread 1.

The second layer 3 is formed by coating on the drug-containing layer 2with a solution obtained on dissolving pellets of a biodegradablepolymer in a solvent added thereto under heating.

In case poly-L-lactic acid is used as the biodegradable polymer, formingthe second layer 3, such a solution is used, which is obtained on mixing1,4-dioxane, as a solvent, to pellets of poly-L-lactic acid, and onstirring the resulting reaction mass under heating to approximately 90°C. for dissolution. In this case, dichloromethane may again be used as asolvent in order to obtain a biodegradable polymer solution employingpoly-L-lactic acid.

After the drug-containing layer 2 is dried, the biodegradable polymersolution, forming the second layer 3, is applied on this drug-containinglayer 2.

The thread 1, on the drug-containing layer 2 of which has been depositedthe biodegradable polymer solution, is then completely dried to give athread for the stent for vessels 20, composed of the drug-containinglayer 2 and the second layer 3, formed only of the biodegradablepolymer, sequentially layered on the thread 1 as shown in FIG. 4.

With the thread for a stent for vessels, obtained on depositing, on thedrug-containing layer 2, the second layer 3, formed only of thebiodegradable polymer of the same sort as that of the thread 1, it ispossible to control the quantity and time period of release of the drugcontained in the drug-containing layer 2.

That is, by constituting the second layer 3, formed only of thebiodegradable polymer, on the drug-containing layer 2, it becomespossible to suppress release of the drug contained in thedrug-containing layer 2, while it also becomes possible to extend thetime period of release of the drug contained in the drug-containinglayer 2.

The time duration of release of the drug contained in thedrug-containing layer 2 becomes possible by changing the thickness ofthe second layer 3, that is, the coating thickness of the biodegradablepolymer solution making up the second layer 3.

Although the thread constituting the thread for the stent for thevessels, according to the present invention, is formed only of thebiodegradable polymer, it is also possible to add the drug to thisthread.

An example of the thread for a stent for vessels 30, comprised of athread 11 containing the drug, is shown in FIG. 5.

The drug-containing thread 11, forming the thread for a stent forvessels 30, shown in FIG. 5, is formed by charging the drug into thehopper, along with pellets, formed of a biodegradable polymer, as thematerial constituting the thread 1, at the time of spinning on the screwextruder. The pellets of the biodegradable polymer, charged into thehopperalong with the drug, are compressed and melted, within a cylinder,as the pellets are heated to a temperature in the vicinity of themelting point Tm or to a temperature not lower than the melting pointand not higher than the thermal decomposition temperature. Within thecylinder is rotated a screw on the outer periphery of which has beenformed a spiral groove. At this time, the drug is melted and mixed intothe melted biodegradable polymer. The biodegradable polymer, melted inthe cylinder, and mixed with the drug, is extruded from a nozzle, set toa temperature not lower than the glass transition temperature Tg, and isspun as the thread 11, commingled with the drug, as it is taken up witha take-up device.

As the material of the biodegradable polymer, constituting the thread11, such a material, the melting point of which is not injurious to thedrug, is used. In case Tranilast is used as the drug, the biodegradablepolymer, melting at a temperature not higher than 220° C., specifically,poly-L-Lactic acid (PLLA), melting at a temperature not higher than 220°C., is used.

The drug-containing layer 2, in the surface region of which is containedthe drug, is provided to the surface of the thread 11, containing thedrug, as in the case of the above-described thread 1 formed only of thebiodegradable polymer, to form the thread for a stent for vessels 30.

As the drug contained in the thread 11 and in the drug-containing layer2, in this thread for a stent for vessels 30, such a drug exhibiting anantithrombotic effect and/or an intimal hyperplasia suppressing effect,is used. As the drug exhibiting intimal hyperplasia suppressing effect,immunosuppressive agent or anti-tumor drugs may be used. The drugcontained in the thread 11 may differ in pharmaceutical efficacy or drugtype from the drug contained in the drug-containing layer 2. Forexample, a drug exhibiting the antithrombotic effect may be contained inone of the thread and the drug-containing layer, while a drug exhibitingintimal hyperplasia suppressing effect may be contained in the other ofthe thread and the drug-containing layer. Specifically, a drugexhibiting the antithrombotic effect may be contained in thedrug-containing layer 2, whilst a drug exhibiting intimal hyperplasiasuppressing effect may be contained in the thread 1.

With use of the drug-containing thread 11, it may be expected to emitrelease the drug for an extended period of time.

In the thread for a stent for vessels, comprised of the drug-containingthread 11, the second layer 3, formed only of the biodegradable polymerof the same sort as the biodegradable polymer constituting the thread11, may be deposited on the surface of the thread 11, as shown in FIG.6. With a thread for a stent for vessels 40, shown in FIG. 6, the secondlayer 3 is formed of the same sort of the biodegradable polymer as thatof the thread 11, so that, if the thread 1 is formed of poly-L-lacticacid (PLLA), the second layer is formed of the same sort ofpoly-L-lactic acid (PLLA). That is, the second layer 3 is formed ofpoly-L-lactic acid (PLLA) which is of the same sort as the material ofthe thread 1, or of poly-L-lactic acid (PLLA) lower in molecular weightthan poly-L-lactic acid (PLLA) forming the thread 1.

The second layer 3 is formed by coating, on the drug-containing layer 2,the solution obtained on dissolving pellets of the biodegradable polymerin a solvent added thereto under heating, as described above.

The threads for a stent for vessels, according to the present invention,described above, are used for forming a stent for vessels, used on beingintroduced into blood vessels, such as coronary artery of the livingbody.

An example of a stent for vessels, formed using a thread for a stent forvessels, according to the present invention, is hereinafter explained indetail.

The stent for vessels may use a thread for a stent for vessels,comprised of a thread formed only of a biodegradable polymer, or athread for a stent for vessels, comprised of a thread containing a drug.In the following, such a case in which the thread for a stent forvessels 10, comprised of the thread 1 formed only of the biodegradablepolymer, is taken as an example for explanation.

A stent for vessels 21, according to the present invention, isconstituted by forming the thread for a stent for vessels 10, describedabove, into a tube, as shown in FIG. 7.

The thread for a stent for vessels 10, formed as explained above, isbent in a zig-zag design in concatenated vee shapes and wound spirallyto constitute a tubular main body portion of the main stent body 13 asshown in FIG. 8. A spirally wound shape of the thread for a stent forvessels 10 is obtained with a side of a bend 14 of the vee shape as ashort portion 14 a and with its opposite side as a long portion 14 b. Bysetting the lengths of the short portion 14 a and the long portion 14 bbetween the bends 14 so as to be approximately equal to each other, theapices of the neighbouring bends 14 are contacted with each other, asshown in FIG. 9. Part or all of the apices of the contacted bends 14 arebonded to one another. The thread for a stent for vessels 10 of the mainbody portion of the main stent body 13 is positively maintained in thestate of keeping the tubular shape by bonding the apices of the bends 14contacting with each other.

The stent 21, constituted using the tubular main body portion of themain stent body 13, is shape-memorized to the size with which it isimplanted in the blood vessel. For realizing this shape memory, as shownin FIG. 10, the stent 21 is equipped on a shaft-like mold frame 101sized to maintain the size of the stent 21 implanted in the vessel ofthe living body, and is heated to a temperature higher than the glasstransition temperature Tg and lower than the melting point of thebiodegradable polymer constituting the thread for a stent for vessels10, so as to be deformed to a size consistent with the size of the moldframe 101. The stent 21 equipped on the mold frame 101 then is cooled,along with the mold frame 101, to a temperature lower than the glasstransition temperature Tg. This affords to the stent 21 the shape memoryproperties so that the stent is fixed in the deformed state.

The stent 21, obtained in this manner, is shape-memorized to thediameter R1 of approximately 3 to 5 mm and to the length L1 of 10 to 15mm, as shown in FIG. 7. This size corresponds to or is larger than thediameter with which the stent is implanted in the blood vessel of theliving body.

This shape-memorized stent 21 is contracted in diameter after it isdismounted from the mold frame 101. This contraction in diameter occursas the main body portion of the main stent body 13 is deformed under amechanical force applied from the outer perimeter of the main bodyportion of the main stent body 13 in the state in which the stent iscooled to a temperature lower than the glass transition temperature Tg.

The stent 21 is contracted in diameter by displacing the bends 14 sothat the opening angle θ1 of the bend 14 will be a smaller opening angleθ2, as shown in FIG. 11. This diameter contraction, achieved bydisplacing the bends 14, is performed by deforming the bends 14 of thethread for a stent for vessels 10 cooled to a temperature lower than theglass transition temperature Tg. At this time, the stent 21 iscontracted in diameter so that the stent 21 can be easily implanted inthe vessel of the living body. For example, in the stent 21,shape-memorized to the diameter R1 of approximately 3 to 5 mm, thediameter is contracted to a diameter R2 of approximately 1 to 2 mm, asshown in FIG. 12.

If the stent 21, contracted in diameter by application of an externalforce, is heated to a temperature higher than the glass transitiontemperature Tg of a biodegradable polymer forming the thread for a stentfor vessels 10, it is relieved of the strain afforded to the bends 14,so that the bend 14 folded to the small opening angle θ2 is opened tothe opening angle θ1 to restore to its original shape-memorized size.That is, the stent 21 on being re-heated to a temperature higher thanthe glass transition temperature Tg is enlarged to its originalshape-memorized size, as shown in FIG. 7.

Meanwhile, the stent 21 for the vessel, according to the presentinvention, is used as it is inserted into the blood vessel, such as thecoronary vessel of the living body, and is enlarged in diameter to theshape-memorized state, when inserted into the blood vessel, to supportits inner wall. It is noted that the thread for a stent for vessels 10,making up the stent 21 for the vessel, is formed of a biodegradablepolymer, with the glass transition temperature Tg lower than 70° C., inorder to restore to its original shape by the temperature equal or closeto body temperature of the living body.

The stent 21, formed by the thread for a stent for vessels 10, which hasthe glass transition temperature Tg lower than 70° C. and which is ableto restore to its original shape by the body temperature of the livingbody, can be heated at a temperature not producing heat damages to theblood vessel of the living body, even if it is heated for enlarging itsdiameter to its shape-memorized state.

With the stent for the blood vessels 21, formed using the thread for astent for vessels 10 according to the present invention, the drug may becarried by the drug-containing layer 2 so as to be positively beadministered to a desired site within the blood vessel. Additionally,with use of the thread for a stent for vessels 10, with the controllablerelease time period, the drug may be emitted to within the blood vesselsfor any desired time period following the implanting of the stent withinthe blood vessels.

If the stent for the blood vessels 21 is formed using the thread for astent for vessels 10, comprised of the thread 1 as the base material andonly the drug-containing layer 2 on the surface thereof, as shown inFIG. 3, a polymer layer may be formed on the surface of the main stentbody 13, formed of the thread for a stent for vessels 10, bent to atubular form, by applying a solution obtained on dissolving thebiodegradable polymer of the same sort as the material making up thethread 1 as the base material. That is, if the thread 1 is formed ofpoly-L-lactic acid (PLLA), the biodegradable polymer layer may be formedof the same sort of poly-L-lactic acid (PLLA).

The biodegradable polymer layer, formed on the surface of the main stentbody 13, may be formed by coating a biodegradable polymer solution,using a coating device, or by immersing the main stent body 13 in thebiodegradable polymer solution.

Since the biodegradable polymer layer is formed on the surface of themain stent body 13, it becomes possible to suppress the amount ofrelease of the drug from the drug-containing layer 2 as well as tocontrol the time of drug release.

The above-described stent for blood vessels is formed of the thread fora stent for vessels 10, comprised of the thread 1 and only thedrug-containing layer 2 on the surface thereof. In a similar manner, thestent for blood vessels may also be formed by the other threads for astent for vessels 20, 30 or 40. With use of these threads 20, 30 or 40,it is possible to form stents for blood vessels exhibiting theproperties owned by these threads 20, 30 and 40.

With the stents, comprised of these threads 20, 30 or 40, the solutionsobtained on dissolving the biodegradable polymers of the same type asthe materials making up the threads 1, 11 as the base material may becoated on the surface of the main stent body unit to provide polymerlayers.

EXAMPLES

Specified examples of the thread for a stent for vessels, according tothe present invention, are hereinafter explained, along with the methodfor manufacture thereof.

Example 1

For forming a thread for a stent for vessels, according to the presentinvention, a thread 1 formed of a biodegradable polymer, as a basematerial, is provided.

The thread 1, used here, is formed by melt-spinning pellets ofpoly-L-lactic acid (PLLA), using a screw extruder. The thread 1, usedfor forming a stent for blood vessels, implanted in a living body, inparticular in a coronary artery of the human being, is a continuouslength of a monofilament with a diameter of approximately 150 μm. Ofcourse, a thread 1 formed by a multifilament, composed of pluralmonofilaments la, unified together, may also be used.

The thread 1 provided is rinsed for removing impurities, such as dustand dirt, affixed to its surface.

The thread 1 is rinsed with ethanol and with distilled water. First, thethread 1 is injected into a washing tank charged with ethanol andagitated at ambient temperature for approximately 20 minutes. Thisrinsing in ethanol under agitation is carried out twice. The thread 1,rinsed with ethanol, is charged into a washing tank charged withdistilled water and rinsed. The thread 1, rinsed with distilled water,is preserved for one day in a vacuum indicator for drying.

As the thread 1 is rinsed, a biodegradable polymer solution, containinga drug, configured for being coated on the surface of the thread 1, isprovided. Here, Tranilast and poly-L-lactic acid are used as a drug andas a biodegradable polymer, respectively.

For forming the biodegradable polymer solution, Tranilast powders andpellets of poly-L-lactic acid of the same weight as the Tranilastpowders are provided.

A suitable amount of 1,4-dioxane, as a solvent, is added into a tankcharged with the pellets of poly-L-lactic acid. The resulting product isheated to 90° C. and agitated to dissolve the pellets of poly-L-lacticacid. When the solvent starts to be vaporized, the solvent is addedlittle by little until the pellets of poly-L-lactic acid are dissolvedcompletely.

When the pellets of poly-L-lactic acid are dissolved completely, aweight amount of the Tranilast powders is added to the reaction systemand agitated. When the solvent starts to be vaporized, the solvent isadded little by little until the Tranilast powders become evenlydispersed in the poly-L-lactic acid solution. The desired biodegradablepolymer solution is obtained by the weighed out amount of the Tranilastpowders becoming dispersed homogeneously.

The poly-L-lactic acid solution, as the Tranilast-containingbiodegradable polymer solution, is coated on the surface of the rinsedthread 1.

The Tranilast-containing poly-L-lactic acid solution, to be coated onthe surface of the thread 1, is mixed at a ratio of 3:1 into1,4-dioxane, as a solvent, and agitated for dilution.

The so-diluted Tranilast-containing poly-L-lactic acid solution isapplied to the surface of the thread 1, using e.g. a brush for coating.At this time, the Tranilast-containing poly-L-lactic acid solution iscoated so that the thickness of the coated thread, having a diameter ofapproximately 150 μm, may come up to approximately 165 μm. That is, thepoly-L-lactic acid solution is coated to a thickness of 7 to 8 μm. Thethread 1, coated with the Tranilast-containing poly-L-lactic acidsolution, is preserved for one day in a vacuum indicator for drying,whereby the solvent 1,4-dioxane is completely vaporized to yield thethread for a stent for vessels 10, on the surface of which has beenformed the drug-containing layer 2, as shown in FIG. 3. At this time,the drug is contained only in poly-L-lactic acid in the drug-containinglayer 2.

Example 2

Another thread for a stent for vessels 10, according to the presentinvention, comprised of a second layer 3, which is deposited on thedrug-containing layer 2, as the first layer, and which is formed only ofthe biodegradable polymer of the same sort as the biodegradable polymerforming the thread 1, is formed by further coating the surface of thethread 1, on the surface of which is formed only the drug-containinglayer 2, with a biodegradable polymer solution.

Since the thread 1 is obtained by melt-spinning pellets of poly-L-lacticacid (PLLA) using a screw extruder, a solution of poly-L-lactic acid isused as the biodegradable polymer solution coated for forming the secondlayer 3.

The solution of poly-L-lactic acid is obtained on adding a suitableamount of 1,4-dioxane, as a solvent, into a tank charged with pellets ofpoly-L-lactic acid, and heating the resulting reaction mass to 90° C.,and agitatin to dissolve the pellets of poly-L-lactic acid.

The solution of poly-L-lactic acid, obtained on dissolution, is coatedon the drug-containing layer 2 configured on the surface of the thread1, using e.g. a brush for coating. The solution of poly-L-lactic acid isapplied at this time so that the thickness of the thread 1, having athickness of approximately 150 μm, will be approximately 165 μm,inclusive of the thickness of the drug-containing layer 2. That is, thepoly-L-lactic acid solution, forming the second layer, is coated to athickness of 7 to 8 μm, inclusive of the thickness of drug-containingpoly-L-lactic acid, forming the drug-containing layer 2. The thread 1,comprised of the drug-containing layer 2 and of the second drug layer 3,formed only of the biodegradable polymer, is preserved for one day in avacuum indicator for drying, whereby the solvent 1,4-dioxane iscompletely vaporized to yield the thread for a stent for vessels 10,comprised of the drug-containing layer 2 and the second drug layer 3,formed only of the biodegradable polymer, as shown in FIG. 4.

In the foregoing, the present invention is applied to a stent for bloodvessels. The present invention may, however, be extensively applied tostents implanted in other vessels in the living body.

The present invention is not limited to the above-described embodiments,explained with reference to the drawings. Instead, a variety of changes,substitutions or equivalents, as may be apparent to those skilled in theart, may be encompassed within the scope of the present invention.

INDUSTRIAL APPLICABILITY

With the thread for a stent for vessels, and the stent for vesselsformed using this thread, according to the present invention, adrug-containing layer is formed by depositing a biodegradable polymersolution of the same sort as the material forming the thread, admixedwith the drug, and hence the drug may be prevented from becomingdetached from the thread, and may positively be carried on its surface.

In addition, drug release for a further extended period of time becomespossible by providing the drug-containing layer and by having the drugcontained in the melt spun thread itself.

Moreover, since the drug may positively be carried on the threadsurface, the drug can be positively administered to a target site in theliving body by forming the stent for vessels with use of such thread.

Since it is possible to control the period for release of the drugcontained in the drug-containing layer formed on the thread surface, thedrug can be released under desirable conditions following implanting thestent for vessels in the living body.

1-34. (canceled)
 35. A thread for a vascular stent, implanted invessels, the thread being formed by melt-spinning a first biodegradablepolymer, wherein a layer of a second biodegradable polymer that containsa drug is formed on a thread surface, and wherein the first and secondbiodegradable polymers are composed of substantially the samebiodegradable polymer.
 36. The thread for a vascular stent according toclaim 35, wherein the layer of second biodegradable polymer is formed bycoating on the thread surface.
 37. The thread for a vascular stentaccording to claim 35, wherein the first and second biodegradablepolymers are composed of an aliphatic polyester.
 38. The thread for avascular stent according to claim 35, wherein said thread is amonofilament obtained by melt-spinning a biodegradable polymer using ascrew extruder and on drawing a resulting thread.
 39. The thread for avascular stent according to claim 35, wherein said thread is amultifilament obtained by melt-spinning a biodegradable polymer using ascrew extruder and on drawing a resulting thread.
 40. The thread for avascular stent according to claim 35, wherein said drug exhibits atleast one of an antithrombotic effect and an intimal hyperplasiasuppressing effect.
 41. The thread for a vascular stent according toclaim 40, wherein said drug exhibiting the intimal hyperplasiasuppressing effect is an immunosuppressive agent or an anticancer agent.42. The thread for a vascular stent according to claim 35 wherein afirst layer of the second biodegradable polymer and a second layerformed only of a third biodegradable polymer that is substantially thesame as the biodegradable polymer are sequentially formed on the threadsurface.
 43. A thread for a vascular stent, implanted in vessels, thethread being formed by mixing a drug into a first biodegradable polymerand by melt-spinning the resulting biodegradable polymer, wherein adrug-containing layer of a second biodegradable polymer that issubstantially the same as the first biodegradable polymer is formed on athread surface.
 44. The thread for a vascular stent according to claim43 wherein said drug-containing layer of said second biodegradablepolymer is formed by coating, on the thread surface, a drug-containingbiodegradable polymer solution that is substantially the same as thebiodegradable polymer constituting said thread.
 45. The thread for avascular stent according to claim 43 wherein the first biodegradablepolymer constituting said thread is aliphatic polyester.
 46. The threadfor a vascular stent according to claim 43 wherein said thread is amonofilament obtained by melt-spinning a drug-containing biodegradablepolymer using a screw extruder and drawing the resulting thread.
 47. Thethread for a vascular stent according to claim 43 wherein said thread isa multifilament obtained by melt-spinning a drug-containingbiodegradable polymer using a screw extruder and drawing the resultingthread.
 48. The thread for a vascular stent according to claim 43wherein said drug exhibits at least one of an antithrombotic effect andan intimal hyperplasia suppressing effect.
 49. The thread for a vascularstent according to claim 48 wherein said drug exhibiting the intimalhyperplasia suppressing effect is an immunosuppressive agent or ananticancer agent.
 50. The thread for a vascular stent according to claim43 wherein a first layer of a drug-containing biodegradable polymer thatis substantially the same as the biodegradable polymer forming thethread and a second layer formed only of a biodegradable polymer that issubstantially the same as the biodegradable polymer forming the threadare sequentially formed on the thread surface.
 51. A vascular stentimplantable in vessels of a living body, comprising: a main stent bodyformed by threads of a biodegradable polymer for a stent for vesselswhich are wound to a tube as each of the threads is bent in a zigzagdesign and is enlarged or contracted in diameter with the bends of thethreads as displacing portions; wherein the threads constituting themain stent body are formed by melt-spinning a biodegradable polymer, anda layer of a biodegradable polymer containing a drug that issubstantially the same as the biodegradable polymer constituting thethreads is formed on the surface of the threads.
 52. The vascular stentaccording to claim 51 wherein said biodegradable polymer constitutingsaid thread is an aliphatic polyester.
 53. The vascular stent accordingto claim 51 wherein said thread is a monofilament obtained bymelt-spinning a biodegradable polymer using a screw extruder and drawingthe resulting thread.
 54. The vascular stent according to claim 51wherein said thread is a multifilament obtained by melt-spinning abiodegradable polymer using a screw extruder and drawing the resultingthread.
 55. The vascular stent according to claim 51 wherein said drugexhibits at least one of an antithrombotic effect and an intimalhyperplasia suppressing effect.
 56. The vascular stent according toclaim 55 wherein said drug exhibiting the intimal hyperplasiasuppressing effect is an immunosuppressive agent or an anticancer agent.57. The vascular stent according to claim 51 wherein a first layer of adrug-containing biodegradable polymer that is substantially the same asthe biodegradable polymer forming the thread and a second layer formedonly of a biodegradable polymer that is substantially the same as thebiodegradable polymer forming the thread are sequentially formed on thethread surface.
 58. The vascular stent according to claim 51 wherein abiodegradable polymer solution that is substantially the same as thebiodegradable polymer constituting said thread is coated on the surfaceof said main stent body.
 59. The vascular stent according to claim 51wherein a biodegradable polymer solution that is substantially the sameas the material constituting said thread is deposited on the surface ofsaid main stent body to form a biodegradable polymer layer.
 60. Avascular stent implantable in vessels of a living body, comprising: amain stent body formed by threads of a biodegradable polymer for a stentfor vessels which are wound to a tube as each of the threads is bent ina zigzag design and is enlarged or contracted in diameter with the bendsof the threads as displacing portions; wherein the threads constitutingthe main stent body are formed by melt-spinning a drug-containingbiodegradable polymer, and a layer of a biodegradable polymer containinga drug that is substantially the same as the biodegradable polymerconstituting the threads is formed on a surface of the threads.
 61. Thevascular stent according to claim 60 wherein said biodegradable polymerconstituting said thread is an aliphatic polyester.
 62. The vascularstent according to claim 60 wherein said thread is a monofilamentobtained by melt-spinning a drug-containing biodegradable polymer usinga screw extruder and drawing the resulting thread.
 63. The vascularstent according to claim 60 wherein said thread is a multifilamentobtained by melt-spinning a drug-containing biodegradable polymer usinga screw extruder and drawing the resulting thread.
 64. The vascularstent according to claim 60 wherein said drug exhibits at least one ofan antithrombotic effect and an intimal hyperplasia suppressing effect.65. The vascular stent according to claim 64 wherein said drugexhibiting the intimal hyperplasia suppressing effect is animmunosuppressive agent or an anticancer agent.
 66. The vascular stentaccording to claim 60 wherein a first layer of a drug-containingbiodegradable polymer that is substantially the same as thebiodegradable polymer forming the thread and a second layer formed onlyof a biodegradable polymer that is substantially the same as thebiodegradable polymer forming the thread are sequentially formed on thethread surface.
 67. The vascular stent according to claim 60 wherein abiodegradable polymer solution that is substantially the same sort asthe biodegradable polymer constituting said thread is coated on thesurface of said main stent body.
 68. The vascular stent according toclaim 60 wherein a solution of a biodegradable polymer that issubstantially the same as the material constituting said thread isdeposited on the surface of said main stent body to form a biodegradablepolymer layer.